Modulation of Dopaminergic Neuronal Excitability by Zinc through the Regulation of Calcium-related Channels
| Autor: | Jun Mo Chung, Jihyun Noh |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Calcium buffering chemistry.chemical_element Calcium Calcium in biology SK channel 03 medical and health sciences Cellular and Molecular Neuroscience Transient receptor potential channel chemistry.chemical_compound 0302 clinical medicine BAPTA Patch clamp recording Voltage-dependent calcium channel Ryanodine receptor Spike frequency Dopamine system Electrophysiology 030104 developmental biology chemistry Biophysics Rat Original Article Neurology (clinical) Calcium-activated non-selective cation 030217 neurology & neurosurgery |
| Zdroj: | Experimental Neurobiology |
| ISSN: | 2093-8144 1226-2560 |
| DOI: | 10.5607/en.2019.28.5.578 |
| Popis: | Depending on the intracellular buffering of calcium by chelation, zinc has the following two apparent effects on neuronal excitability: enhancement or reduction. Zinc increased tonic activity in the depolarized state when neurons were intracellularly dialyzed with EGTA but attenuated the neuronal activity when BAPTA was used as an intracellular calcium buffer. This suggests that neuronal excitability can be modulated by zinc, depending on the internal calcium buffering capacity. In this study, we elucidated the mechanisms of zinc-mediated alterations in neuronal excitability and determined the effect of calcium-related channels on zinc-mediated alterations in excitability. The zinc-induced augmentation of firing activity was mediated via the inhibition of small-conductance calcium-activated potassium (SK) channels with not only the contribution of voltage-gated L-type calcium channels (VGCCs) and ryanodine receptors (RyRs), but also through the activation of VGCCs via melastatin-like transient receptor potential channels. We suggest that zinc modulates the dopaminergic neuronal activity by regulating not only SK channels as calcium sensors, but also VGCCs or RyRs as calcium sources. Our results suggest that the cytosolic calcium-buffering capacity can tightly regulate zinc-induced neuronal firing patterns and that local calcium-signaling domains can determine the physiological and pathological state of synaptic activity in the dopaminergic system. |
| Databáze: | OpenAIRE |
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